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Plastic waste, especially positively buoyant polymers known as polyolefins, are a major component of floating debris in the marine environment. While plastic colonisation by marine microbes is well documented from environmental samples, the succession of marine microbial community structure over longer time scales (> > 1 month) and across different types and shapes of plastic debris is less certain. We analysed 16S rRNA and 18S rRNA amplicon gene sequences from biofilms on polyolefin debris floating in a flow-through seawater tank in Hawaii to assess differences in microbial succession across the plastic types of polypropylene (PP) and both high-density polyethylene (HDPE) and low-density polyethylene (LDPE) made of different plastic shapes (rod, film and cube) under the same environmental conditions for 1 year. Regardless of type or shape, all plastic debris were dominated by the eukaryotic diatom Nitzschia, and only plastic type was significantly important for bacterial community structure over time (p = 0.005). PE plastics had higher differential abundance when compared to PP for 20 bacterial and eight eukaryotic taxa, including the known plastic degrading bacterial taxon Hyphomonas (p = 0.01). Results from our study provide empirical evidence that plastic type may be more important for bacterial than eukaryotic microbial community succession on polyolefin pollution under similar conditions.

Background Due to the ability of metal ions to cross the blood–brain barrier, there has been interest in analyzing cerebrospinal fluid (CSF) for trace element concentrations to investigate possible correlations with neurodegenerative diseases. In this study, Sarstedt polypropylene CSF collection tubes were analyzed to determine the contamination levels of aluminum, titanium, chromium, manganese, cobalt, nickel, molybdenum, gadolinium, vanadium, arsenic, cadmium, mercury, lead, thallium, selenium, copper, zinc, and iron. Methods Sarstedt polypropylene CSF collection tubes from 2 separate lots (n = 10 per lot) were filled with a 2 mL aliquot of a CSF pool with known element concentrations. After 24 hours of leaching at room temperature, all 18 elements were analyzed via inductively coupled plasma mass spectrometry (ICP-MS). Results were subtracted from the initial pool concentration to determine contamination levels. Results No detectable contamination above the assay limit of detection was found in 11 analytes. Molybdenum and selenium contamination was measured in all tubes, and aluminum, titanium, manganese, thallium, and zinc had minimal levels of sporadic detectable contamination in 25% or fewer of the tubes tested. Conclusions Sarstedt polypropylene CSF tubes are an acceptable collection tube for the analysis of most assessed metals in CSF. [ABSTRACT FROM AUTHOR]

Many reactive intermediates leading to high value molecules are biosynthesised by multifunctional enzymes in Actinobacteria. Herein we report the workings of a cryptic iterative polyketide synthase (iPKS) from the marine microorganism Rhodococcus erythropolis PR4. The iPKS generates extended polyenes up to C22 nonaenes, preluding novel chemistry and biology. [ABSTRACT FROM AUTHOR]

The all-trans and all-cis polyenes homodisubstituted at the ends were calculated at the B3LYP/6-31G** level. The disubstitution gives rise to three end-types of the conformers: trans-trans, trans-cis, and cis-cis, denoted as EE, EZ, and ZZ. The symmetry of the EE or ZZ all-cis isomers depended on the double bond parity. Twelve substituents used: H, BeH, BH2, BF2, Br, CH3, Cl, CN, F, NH2, NO2, OH, and SiH3 were chosen to exhibit different σ- and π-electron donating and electron withdrawing properties. For polyenes composed up to ca. 20 C-atoms, the π-electron donating and withdrawing character of the end groups matters and differently acting substituents play significantly different roles. Unexpectedly, the intramolecular interactions between the substituents and the neighboring chain CH groups near appeared more decisive for the compound's stability than the substituent electron donating/withdrawing properties. The substituent-chain interplay was consonant in the all-trans and all-cis polyenes. Still, they were always more destabilizing in the latter than in all-trans isomers. [ABSTRACT FROM AUTHOR]

Candida albicans, the most common opportunistic pathogenic fungus, is also the main pathogenic organism for oral candidiasis. This condition is particularly prevalent among the elderly, children, and individuals undergoing radiotherapy or suffering from HIV. The lack of new antifungal drugs, and drug resistance coupled with the side effects of current antifungal agents have increased the challenges of clinical antifungal therapies. Polyenes, including amphotericin B and nystatin, are clinical fungicidal drugs, however, their side effects and low solubility have limited their clinical applications. Here, we identified that moxidectin, a novel approved antiparasitic agent, could synergize with both amphotericin B and nystatin to inhibit the growth and biofilm formation of Candida albicans including 60 clinical isolates. The transcriptome and RT-PCR analysis indicated that moxidectin activated the biosynthesis pathway of ergosterol, the direct target of polyenes, further being verified by the loss of the synergistic activities with polyenes against ergosterol pathway mutants, including Δ/Δerg3, Δ/Δerg11 and Δ/Δerg3 Δ/Δerg11. Moxidectin was then confirmed to elevate the ergosterol biosynthesis levels of C. albicans and enhance the binding between cells and polyenes. In a mouse oral candidiasis model, moxidectin combined with low dosages of polyenes to significantly reduce the infection area, colonization of C. albicans and the inflammatory degree of tongue mucosa. Our study originally demonstrated that moxidectin could activate the ergosterol biosynthesis then elevate the ergosterol contents to enhance the antifungal effects of polyenes against C. albicans and its infections. Moxidectin can serve as the candidate potentiator of polyenes for further clinical practice. Key points: • Moxidectin synergized with polyenes against Candida albicans. • Moxidectin activated the ergosterol biosynthesis of Candida albicans. • Moxidectin combined with polyenes to effectively combat oral candidiasis in mice. [ABSTRACT FROM AUTHOR]

Chronic postoperative pain is associated with inguinal hernia mesh repair. The aim of the present study is to evaluate the surgical outcomes and cost-effectiveness analysis of inguinal repair using fixed sutured, self-gripping and self-adhering mesh. A non-randomized single-centre observational study was conducted with a sample size of 159 inguinal hernia mesh repair from October 2012 to December 2014. Patients with primary unilateral inguinal hernia were treated with sutured mesh polypropylene, self-gripping and self-adhering mesh by two consultant surgeons. All patients were followed prospectively for a period of 5 years. Mean operating time was significantly shorter in the self-gripping and self-adhering group than in sutured mesh (self-gripping vs sutured: p<0.05; self-adhering vs sutured: p<0.05). At two early time points, the pain level was significantly lower in patients with no sutured meshes (self-gripping vs sutured: p<0.01; self-adhering vs sutured: p<0.01). Chronic pain did not significantly differ between groups. Overall, of recurrence were 2.5%, without significant difference between groups. In this non-randomized comparative study, the use of self-adhesive and self-gripping meshes in inguinal hernia repair will reduce early postoperative pain. However, with their uses, there is no evidence of reduction on postoperative chronic pain. Despite self-fixating meshes are more expensive, our cost-effective analysis compared with standard sutured mesh showed advantage in terms of cost as their use. [ABSTRACT FROM AUTHOR]

Literature continues to be ambiguous on the type of mesh to be used in laparoscopic incisional and ventral hernia repair. This study presents non-randomised comparison of polypropylene and covered mesh in laparoscopic incisional and ventral hernia repair. Patients undergoing laparoscopic ventral hernia repair from 2004 to 2018 were divided into two groups, i.e. polypropylene or covered mesh. Laparoscopic ventral hernia repair was done following a standard protocol. Patient outcomes were measured in terms of re-exploration, wound/ mesh infection, seroma, subacute intestinal obstruction, fistula formation and recurrence. Patients were followed up regularly. Laparoscopic repair was performed in 527 patients. Conversion to open repair was done in 30 patients. Polypropylene mesh was used in 175 patients and covered mesh in 352 patients. Subacute intestinal obstruction was seen in 12 patients (6.9%) in polypropylene group and in 18 patients (5.1%) in covered mesh group. There were 28 recurrences, 11 (6.2%) in polypropylene group and 17 (4.8%) in covered mesh group. The median duration of recurrence was 2 years with a range of 16–48 months. Outcomes with polypropylene mesh were comparable to covered mesh for laparoscopic ventral hernia repair with regards to early and late post-operative outcomes. The incidence of fistulisation and obstruction was also similar between the two groups. It is safe to use polypropylene mesh in situations where covered mesh is not affordable or available especially in low resource countries. [ABSTRACT FROM AUTHOR]

This study explores the reaction mechanism between [(BDI)Ca(μ‐H)]2 and cyclopentadiene (C5H6). By analyzing the reaction pathways, it is found that compared with the traditional CaH/CC insertion reaction of polyenes with [(BDI)Ca(μ‐H)]2, C5H6 is more inclined to undergo a CaH/CH2 dehydrogenation reaction, resulting in more stable cyclopentadienyl complexes. The subsequent reactions also tend to continue with dehydrogenation to form dimeric complexes. The aromatization process of C5H6 is a key factor driving this reaction trend. This result provides a new perspective for understanding the catalytic behavior of calcium hydride derivatives and can help in the design and synthesis of new catalysts and functional materials based on such compounds. [ABSTRACT FROM AUTHOR]

Recently, polyacetylene (PA) has been receiving renewed scientific attention due to its electrical properties, potentially useful for energy applications (e.g., fabrication of electrodes for rechargeable batteries and supercapacitors), and unique functional characteristics (e.g., gas trap, oxygen scavenger, EMI shielding, etc.). This chemical compound can be obtained in the form of polyacetylene–PVOH copolymers simply through the chemical dehydration of poly(vinyl alcohol) (PVOH), which is a very common type of polymer, widely used in packaging and other technological areas. This very inexpensive chemical reaction for the large-scale synthesis of PA/polyvinylenes is investigated by reacting PVOH with sulfuric acid at room temperature. In this process, PVOH, shaped in the form of a film, is dipped in sulfuric acid (i.e., H2SO4 at 95%–97%) and, after complete chemical dehydration, it is mechanically removed from the liquid phase by using a nylon sieve. The reduction process leads to a substantial PVOH film conversion into PA, as demonstrated by infrared spectroscopy (ATR mode). Indeed, the ATR spectrum of the reaction product includes all the characteristic absorption bands of PA. The reaction product is also characterized through the use of UV–Vis spectroscopy in order to evidence the presence in the structure of conjugated carbon–carbon double bonds of various lengths. Differential scanning calorimetry (DSC) and thermogravimetric analysis are used to investigate the PA solid-state cis–trans isomerization and thermal stability in air and nitrogen, respectively. XRD is used to verify the polymer amorphous nature. [ABSTRACT FROM AUTHOR]

Decades of previous efforts to develop renal-sparing polyene antifungals were misguided by the classic membrane permeabilization model1. Recently, the clinically vital but also highly renal-toxic small-molecule natural product amphotericin B was instead found to kill fungi primarily by forming extramembraneous sponge-like aggregates that extract ergosterol from lipid bilayers2-6. Here we show that rapid and selective extraction of fungal ergosterol can yield potent and renal-sparing polyene antifungals. Cholesterol extraction was found to drive the toxicity of amphotericin B to human renal cells. Our examination of high-resolution structures of amphotericin B sponges in sterol-free and sterol-bound states guided us to a promising structural derivative that does not bind cholesterol and is thus renal sparing. This derivative was also less potent because it extracts ergosterol more slowly. Selective acceleration of ergosterol extraction with a second structural modification yielded a new polyene, AM-2-19, that is renal sparing in mice and primary human renal cells, potent against hundreds of pathogenic fungal strains, resistance evasive following serial passage in vitro and highly efficacious in animal models of invasive fungal infections. Thus, rational tuning of the dynamics of interactions between small molecules may lead to better treatments for fungal infections that still kill millions of people annually7,8 and potentially other resistance-evasive antimicrobials, including those that have recently been shown to operate through supramolecular structures that target specific lipids9.

We report biosynthetic pathways that can synthesize and transform conjugated octaenes and nonaenes to complex natural products. The biosynthesis of (-)-PF1018 involves an enzyme PfB that can control the regio-, stereo-, and periselectivity of multiple reactions starting from a conjugated octaene. Using PfB as a lead, we discovered a homologous enzyme, BruB, that facilitates diene isomerization, tandem 8π-6π-electrocyclization, and a 1,2-divinylcyclobutane Cope rearrangement to generate a new-to-nature compound.

The equation-of-motion coupled-cluster singles and doubles method with double electron attachment (EOM-DEA-CCSD) is capable of computing reliable energies, wave functions, and first-order properties of excited states in diradicals and polyenes that have a significant doubly excited character with respect to the ground state, without the need for including the computationally expensive triple excitations. Here, we extend the capabilities of the EOM-DEA-CCSD method to the calculations of a multiphoton property, two-photon absorption (2PA) cross sections. Closed-form expressions for the 2PA cross sections are derived within the expectation-value approach using response wave functions. We analyze the performance of this new implementation by comparing the EOM-DEA-CCSD energies and 2PA cross sections with those computed using the CC3 quadratic response theory approach. As benchmark systems, we consider transitions to the states with doubly excited character in twisted ethene and in polyenes, for which EOM-EE-CCSD (EOM-CCSD for excitation energies) performs poorly. The EOM-DEA-CCSD 2PA cross sections are comparable with the CC3 results for twisted ethene; however, the discrepancies between the two methods are large for hexatriene. The observed trends are explained by configurational analysis of the 2PA channels. [ABSTRACT FROM AUTHOR]

Conjugated and non-conjugated polyenes are important substructures and are often found in biologically active compounds and natural products. Their preparation often needs multiple steps or iterative reactions and as a result, they have poor step economies. In this feature article, we show a new methodology to prepare these substructures by combinations of cross-dimerisation giving borylated polyenes and subsequent cross-coupling reactions. This divergent reaction strategy allows for the opportunity to access many bioactive compounds and natural products as well as some electronic materials. [ABSTRACT FROM AUTHOR]

Inguinal hernia repair is one of the most commonly performed operations in general surgery, with several surgical techniques to do it. The laparoscopic transabdominal preperitoneal (TAPP) approach has gained wide popularity in recent years. Introduction of 3D mesh is one of the recent advances in inguinal hernia treatment. The aim of this study is to evaluate the efficacy of 3D mesh compared to conventional polypropylene mesh in laparoscopic TAPP repair of inguinal hernia. A prospective study was carried out on 60 patients, 30 patients in each group. They underwent laparoscopic TAPP repair of inguinal hernia with 3D mesh or polypropylene mesh over a period of one year. The data analysed included demographic data, mesh spreading time, operative time, post-operative pain, post-operative complications, hospital stay, and chronic groin pain. Follow-up period was 1 year. The mesh spreading time was shorter in 3D mesh 7.32 SD 2.98 vs 12.68 SD 3.59 min, in polypropylene mesh (p = 0.001). The postoperative pain score was higher in polypropylene mesh 4.93 SD 0.87 vs 3.97 SD 0.81 (p = 0.001). The incidence of postoperative complications was not significantly different between the two groups apart from the frequency of chronic pain after 6 months, which was significantly higher in polypropylene mesh group 5 (16.7%) vs 1 (3.3%) (p = 0.02). The non-fixation of 3D mesh in laparoscopic TAPP inguinal hernia repair is a feasible, safe option for surgical treatment of inguinal hernia with shorter mesh spreading time and reduced post-operative pain and chronic pain, without increasing complications nor recurrence rates. [ABSTRACT FROM AUTHOR]

Polyenes are a class of organic compounds well known for their potent antifungal properties. They are effective due to their ability to target and disrupt fungal cell membranes by binding to ergosterol and forming pores. Despite their effectiveness as antifungal drugs, polyenes have several limitations, such as high toxicity to the host cell and poor solubility in water. This has prompted ongoing research to develop safer and more efficient derivatives to overcome such limitations while enhancing their antifungal activity. In this review article, we present a thorough analysis of polyene derivatives, their structural modifications, and their influence on their therapeutic effects against various fungal strains. Key studies are discussed, illustrating how structural modifications have led to improved antifungal properties. By evaluating the latest advancements in the synthesis of polyene derivatives, we highlight that incorporating amide linkers at the carboxylic moiety of polyene molecules notably improves their antifungal properties, as evidenced by derivatives 4, 5, 6G, and 18. This review can help in the design and development of novel polyene-based compounds with potent antifungal activities. [ABSTRACT FROM AUTHOR]

Background: Mediumweight (40–60 g/m2) polypropylene (MWPP) mesh has been shown to be safe and effective in CDC class II–III retromuscular ventral hernia repairs (RMVHR). However, MWPP has the potential to fracture, and it is possible that heavyweight (> 75 g/m2) polypropylene mesh has similar outcomes in this context. However, there is limited data on HWPP mesh performance in clean-contaminated and contaminated scenarios. We aimed to compare HWPP to MWPP mesh in CDC class II–III wounds during open RMVHR. Methods: The Abdominal Core Health Quality Collaborative database was retrospectively queried for a cohort of patients who underwent open RMVHR with MWPP or HWPP mesh placed in CDC class II/III wounds from 2012 to 2023. Mesh types were compared using a 3:1 propensity score-matched analysis. Covariates for matching included CDC classification, BMI, diabetes, smoking within 1 year, hernia, and mesh width. Primary outcome of interest included wound complications. Secondary outcomes included reoperations and readmissions at 30 days. Results: A total of 1496 patients received MWPP or HWPP (1378 vs. 118, respectively) in contaminated RMVHR. After propensity score matching, 351 patients remained in the mediumweight and 117 in the heavyweight mesh group. There were no significant differences in surgical site infection (SSI) rates (13.4% vs. 14.5%, p = 0.877), including deep SSIs (0.3% vs. 0%, p = 1), surgical site occurrence rates (17.9% vs. 22.2%, p = 0.377), surgical site occurrence requiring procedural intervention (16% vs. 17.9%, p = 0.719), mesh removal (0.3% vs. 0%, p = 1), reoperations (4.6% vs. 2.6%, p = 0.428), or readmissions (12.3% vs. 9.4%, p = 0.504) at 30 days. Conclusion: HWPP mesh was not associated with increased wound morbidity, mesh excisions, reoperations, or readmissions in the early postoperative period compared with MWPP mesh in open RMVHR for CDC II/III cases. Longer follow-up will be necessary to determine if HWPP mesh may be a suitable alternative to MWPP mesh in contaminated scenarios. [ABSTRACT FROM AUTHOR]

This article presents a comprehensive review of the characteristics, phytochemical profile and health effects of chia seeds. Chia seeds belong to the Lamiaceae family, and are small, oval and colored seeds that grow in tropical and temperate climates. Chia seeds are rich in protein, fiber, minerals, phenolic compounds and polyunsaturated fatty acids. These nutrients give chia seeds functional properties such as antioxidant, antiinflammatory, hypolipidemic, hypoglycemic and prebiotic. Chia seeds may play a potential role in the prevention and treatment of chronic diseases such as cardiovascular diseases, diabetes, obesity, digestive system diseases and cancer. Chia seeds can be consumed whole, ground into flour or extracted into oil and added to various foods. Moreover, chia seeds have technological functions such as water retention, emulsification and viscosity enhancement in the food industry. Chia seeds have become a popular functional food in recent years and are being researched. However, more clinical studies and meta-analysis studies are needed on the health effects of chia seeds. [ABSTRACT FROM AUTHOR]

Context: Due to advances in synthesizing lower-dimensional materials, there is the challenge of finding the wave equation that effectively describes quantum particles moving on 1D and 2D domains. Jensen and Koppe and Da Costa independently introduced a confining potential formalism showing that the effective constrained dynamics is subjected to a scalar geometry-induced potential; for the confinement to a curve, the potential depends on the curve's curvature function. Method: To characterize the π electrons in polyenes, we follow two approaches. First, we utilize a weakened Coulomb potential associated with a spiral curve. The solution to the Schrödinger equation with Dirichlet boundary conditions yields Bessel functions, and the spectrum is obtained analytically. We employ the particle-in-a-box model in the second approach, incorporating effective mass corrections. The π - π ∗ transitions of polyenes were calculated in good experimental agreement with both approaches, although with different wave functions. [ABSTRACT FROM AUTHOR]

A complex evaluation of antimicrobial activities of microalgae, including those relevant to wastewater treatment (WWT), in light of the integrated biorefinery concept, is performed. An example of this concept is linking a commercial microalgal system to plants, factories, or farms that emit polluted wastewater (WW). The microalgae would not only metabolize the pollutants—such as nitrogen (N) and phosphorus (P)—from the WW, thus fueling their biomass, but they would exert an antibacterial effect against the pathogenic bacteria there. The biomass then could be harvested and used for biofertilizers, biofuels, and bioplastics and might possibly be utilized as animal feed, antimicrobial and other pharmaceutical agents. A large amount of the research on the antimicrobial activity and WWT potential focuses on the families Chlorellaceae and Scenedesmaceae, which are also some of the most commercially used strains of microalgae. For that reason, they are the species chosen for the current review. Furthermore, the increasing antimicrobial resistance necessitates the search for antibiotic alternatives, and the antibacterial and antifungal activity of Chlorellaceae and Scenedesmaceae is very promising. Microalgae are rich in antibacterial compounds like polyunsaturated fatty acids (PUFAs), polysaccharides, carotenoids, proteins, etc., and for that reason, their extracts possess antimicrobial effects. The in vitro antimicrobial activity of Chlorellaceae and Scenedesmaceae families has varied in a broad range from low to strong activity or no effect. Several strains have fulfilled the criteria for outstanding and high activity, especially C. vulgaris and other Chlorellaceae spp., with an effect equal to or better than the control antibiotics. There were several strains with minimum inhibitory concentrations (MIC) below 80 µg/mL and even 10 and 1.5 µg/mL; some species also had inhibition zones (IZ) over 30 mm, even as high as 48 mm. In vivo results are also promising but scarce, and all this warrants further in vivo and in situ studies—from animal models to clinical and environmental trials. Altogether, important data in the light of the circle economy, the urgent necessity to decrease CO2 emissions to fight climate change, and to curb the harmful influence of future pandemics are presented. This review paves the way for further utilizing the total potential of a microalgal system. [ABSTRACT FROM AUTHOR]

The accuracy of describing the geometry of polyenes in their ground electronic state by various methods is examined. To achieve high accuracy, it is proposed to use the SCS-MP2 method, taking into account the correlation of all electrons, including core ones, and using the cc-pwCVTZ atomic basis. It is shown that, when using this approach, errors in the lengths of C–C bonds do not exceed 0.003 Å. The use of the RIJCOSX and DLPNO approximations speeds up calculations without significantly increasing the errors in bond lengths, but allows the proposed approach to be used to describe such large systems as carotenoids. [ABSTRACT FROM AUTHOR]

Psittacofulvins are polyenal dyes responsible for coloring parrot feathers and protecting them against photo-oxidation, harmful radicals, and bacterial degradation. To explain the unusual properties of these compounds, the thermodynamic and global chemical activity descriptors characterizing four natural and three synthetic psittacofulvins, as well as their hydroxyl, carboxyl and dialdehyde derivatives, were determined. To this aim, the DFT method at the B3LYP/QZVP theory level and the C-PCM solvation model were used. The calculations enabled the selection of the projected compounds for the greatest bioactivity and potential applicability as multifunctional ingredients in medicines, cosmetics, supplements, and food, in which they may play a triple role as preservative, radical scavenger, and coloring agent. The results obtained provide arguments for the identification of a fifth psittacofulvin within the parrot feather pigment, characterized by ten conjugated double bonds (docosadecaenal). [ABSTRACT FROM AUTHOR]

In recent years, a significant number of infections have been attributed to non-albicidal Candida species (NAC), mainly due to the increasing resistance of NAC to antifungal agents. As only a few antifungal agents are available (azoles, echinocandins, polyenes, allylamines and nucleoside analogues), it is very important to look for possible alternatives to inhibit resistant fungi. One possibility could be essential oils (EOs), which have been shown to have significant antifungal and antibacterial activity. Therefore, in this study, the efficacy of 12 EOs and their combinations was evaluated against four yeasts of the genus Candida (C. albicas, C. glabrata, C. tropicalis and C. parapsilosis). GC-MS and GC-MS FID techniques were used for the chemical analysis of all EOs. VITEK-2XL was used to determine the antifungal susceptibility of the tested Candida spp. strains. The agar disc diffusion method was used for primary screening of the efficacy of the tested EOs. The broth dilution method was used to determine the minimum inhibitory concentrations (MICs) of the most potent EOs. After MIC cultivation, the minimum fungicidal concentration (MFC) was determined on Petri dishes (60 mm). The synergistic effect of combined EOs was evaluated using the checkerboard method and expressed as a fractional inhibitory concentration index (FICI). The results showed that ginger > ho-sho > absinth > dill > fennel > star anise > and cardamom were the most effective EOs. For all Candida species tested, the synergy was mainly observed in these combinations: ginger/fennel for C. albicans FICI 0.25 and C. glabrata, C. tropicalis and C. parapsilosis FICI 0.5 and absinth/fennel for C. albicans FICI 0.3125, C. tropicalis FICI 0.3125 and C. parapsilosis FICI 0.375. Our results suggest that the resistance of fungal pathogens to available antifungals could be reduced by combining appropriate EOs. [ABSTRACT FROM AUTHOR]

The conversion of polyolefins to monomers would create a valuable carbon feedstock from the largest fraction of waste plastic. However, breakdown of the main chains in these polymers requires the cleavage of carbon-carbon bonds that tend to resist selective chemical transformations. Here, we report the production of propylene by partial dehydrogenation of polyethylene and tandem isomerizing ethenolysis of the desaturated chain. Dehydrogenation of high-density polyethylene with either an iridium-pincer complex or platinum/zinc supported on silica as catalysts yielded dehydrogenated material containing up to 3.2% internal olefins; the combination of a second-generation Hoveyda-Grubbs metathesis catalyst and [PdP(tBu)3(μ-Br)]2 as an isomerization catalyst selectively degraded this unsaturated polymer to propylene in yields exceeding 80%. These results show promise for the application of mild catalysis to deconstruct otherwise stable polyolefins.

Biodegradable solid-phase poly(vinyl alcohol)/carboxymethyl cellulose composites, which are promising to be used in pharmaceutics, agriculture, and chemical industry, have been obtained by an environmentally friendly method of "mild" mechanochemical activation without solvents and crosslinking agents. Air-dry mixtures of poly(vinyl alcohol) and carboxymethyl cellulose taken in mass ratios of 2 : 1, 1 : 1, and 1 : 2 have been subjected to a shock–shear action for 3 and 5 min (mechanical energy doses of 0.74 and 1.24 kJ/g) using an IVS-4 vibrating grinder (1500 rpm; 23.4 Hz; 0.55 kW; sample weight, 50 g; grinding bodies-to-sample mass ratio, 44 : 1). The mechanically activated samples in the form of medium powders (bulk density within a range of 600–1000 kg/m3) have been studied by the methods of scanning electron microscopy, differential scanning calorimetry, thermogravimetry, IR spectroscopy, optical microscopy, pycnometry, turbidimetry, and gravimetry. It has been found that the mechanochemical activation of an equimass mixture of poly(vinyl alcohol) and carboxymethyl cellulose at a mechanical energy dose of 1.24 kJ/g yields polymer solutions with a concentration of 1 g/dL that are rather transparent in the visible region (turbidity of 0.14 cm–1) and stable for 96 h. It has been revealed that, when being dried at 25°C, poly(vinyl alcohol) crystallizes from aqueous 1 and 2 g/dL solutions to form dendrites or crystallites after treatment at mechanical energy doses of 0.74 and 1.24 kJ/g, respectively. Polymer films of the composites have a complex morphology that includes dendritic and axialite crystalline forms. It has been found that the mechanochemical treatment stimulates the formation of crystalline forms of polymers, changes their intermolecular interaction, and affects the hydroxyl and ether groups of carboxymethyl cellulose, as well as the hydroxyl groups of poly(vinyl alcohol). [ABSTRACT FROM AUTHOR]

Background: While barbed sutures have been extensively utilized in other disciplines, they have not been widely adopted in cardiac surgery. The lack of safety and feasibility data has limited its use within the field. To aide in the further understanding of how cardiac surgeons can use barbed sutures, we sought to develop a high-pressure in vitro simulation model. We compared knotless barbed sutures in a highly pressurized anastomosis to conventional sutures. Methods: Ten specimens in total were utilized in prosthesis anastomosis, using 34 mm Gelweave Plexus (Terumo Aortic, Sunrise, FL 33325, USA) and 34 mm Hemabridge (Intergard Woven Hemabridge, Getinge, Göteborg, Sweden). Five models of size 3-0 barbed suture anastomoses using non-absorbable, barbed, self-retaining, monofilament polypropylene sutures (Filbloc® 3-0, Assut Europe, Rome, Italy) were compared against five conventional anastomoses using size 4-0 polypropylene monofilament (Ethicon, USA). The systems were connected using a novel-designed extracorporeal circulation system. Pressure was rapidly increased in the specimen to a mean pressure of 300–350 mmHg, running then for a minimum of 48 hours to assess anastomosis strength and endurance. Results: No anastomotic dehiscence or rupture was recorded. Complex, angular anastomosis required extra stitch leakage sutures in both conventional and barbed suture specimens. Conclusion: Using knotless barbed sutures with an additional self-locking maneuver for prosthesis-prosthesis anastomosis in cardiac surgery is feasible in an in vitro model under long term, high-mean pressure when compared to conventional sutures. In vivo trials should be performed to further validate the in vitro findings. [ABSTRACT FROM AUTHOR]

Desmoid tumors (DTs) are rare, locally aggressive tumors. When left untreated, DT can rapidly proliferate and occupy a significant portion of the anterior abdomen, making postresection reconstruction challenging. We present a 32‑year‑old female with a previous history of cesarean section and a 10‑month history of two rapidly growing anterior abdominal wall (AAW) masses. There was no clinical or radiologic evidence of distant metastases. Abdominopelvic computed tomography scan showed no intra‑abdominal extension. She had a wide local excision of the masses using an “abdominoplasty” technique and reconstruction of the extensive musculofascial defect with fascia lata grafts and polypropylene mesh. Ahistologic diagnosis of desmoid‑type fibromatosis was made. The patient is scheduled for adjuvant radiotherapy and desires future pregnancies. This case report highlights the reconstructive considerations and challenges associated with surgical resection of huge AAW DT in an oncoplastic unit in a low‑ and middle‑income country. [ABSTRACT FROM AUTHOR]

Sequential C−H functionalization of molecules containing multiple C−H bonds can efficiently lead to structural diversity. Herein we present the first chelation‐assisted sequential α‐/β‐C−H functionalization of E‐styrenes with simple alkenes and alkynes in excellent regio‐ and stereo‐selectivity. The process involves α C−H functionalization by six‐membered exo‐cyclopalladation to result in tri‐ and tetrasubstituted 1,3‐dienes and β C−H functionalization through seven‐membered endo‐cyclopalladation to produce tetra‐ and pentasubstituted 1,3,5‐trienes in up to 97 % yield with up to >99/1 E/Z selectivity, both enabled by the chelation assistance of pyrazinamide. The protocol is demonstrated to be widely applicable, tolerant to a wide range of functional groups and bioactive fragments, and suitable for gram‐scale synthesis as well as one‐pot and two step preparation of trienes. Mechanistic experiments and density functional theory (DFT) calculations were performed to elucidate the selectivity and reactivity. [ABSTRACT FROM AUTHOR]

A new C22 polyacetylene, erysectol A (1), and seven isoprenylated pterocarpans, phaseollin (2), phaseollidin (3), cristacarpin (4), (3′R)-erythribyssin D/(3′S)-erythribyssin D (5a/5b) and dolichina A/dolichina B (6a/6b) were isolated from the twigs and leaves of Erythrina subumbrans. Their structures were determined based on their NMR spectral data. Except for 2–4, all the other compounds were isolated from this plant for the first time. Erysectol A was the first reported C22 polyacetylene from plants. Polyacetylene was isolated from Erythrina plants for the first time. [ABSTRACT FROM AUTHOR]

The solvent-dependent intensity changes in the first UV/Vis absorption band of the three polyenes DPH, DPHb, and ttbP3 dissolved in a hydrocarbon solvent with temperature allow for the conclusion that, at temperatures above 233 K, the two phenyl groups of DPH are rotated out-of-plane to yield a non-coplanar molecular structure. This leads to the conclusion that DPH becomes increasingly less coplanar as the temperature rises above 233 K. When the phenyl groups rotate out-of-plane, the polarizability decreases, and the energy of the first electronic transition increases by an extra value. Therefore, below 233 K, the correlation lines between the absorption energy of the 0–0 component of the UV/Vis absorption band and the solvent polarizability, as measured by the SP values, show bilinear behavior. The unexpected behavior shown by DPH dissolved in tetrachloro- and dichloromethane is discussed. We dedicate this research as a tribute to the very important contribution to the solvent effect made by Prof. Christian Reichardt and also to his generous and altruistic scientific help that he has always shown. [ABSTRACT FROM AUTHOR]

A number of antifungal drugs are based on polyene macrolides that cause severe side effects. Most of these compounds contain a single aminodeoxysugar, D-mycosamine. Toxicity can be reduced by increasing the extent of glycosylation. The aromatic heptaene 67-121C and two analogues of the degenerate heptaene nystatin have a second sugar attached to the C4′ hydroxyl of mycosamine. Another nystatin analogue has L-digitoxose as a second sugar attached to C35 on the macrolactone ring. The pentaene selvamicin has 4-O-methyl-L-digitoxose at C27, the equivalent position. To assist the production of new antifungals by synthetic biology, we explore further the utility of three classes of polyene glycosyltransferase: extending glycosyltransferases that form disaccharide-containing polyenes, glycosyltransferases that add the L-digitoxose sugars of nystatin A3 and selvamicin, and mycosaminyltransferases that add the primary aminodeoxysugar. In addition, we combine enzymatic hyperglycosylation with a known chemical method for adding sugars to the C3′ amino group of mycosamine. This was used to convert the disaccharide-containing 67-121C heptaene to forms containing branched trisaccharide or tetrasaccharide chains. These analogues are of interest for testing as anti-Leishmania drugs. [ABSTRACT FROM AUTHOR]

A new manumycin-type natural product named pacificamide (1) and its candidate biosynthetic gene cluster (pac) were discovered from the marine actinobacterium Salinispora pacifica CNT-855. The structure of the compound was determined using NMR, electronic circular dichroism, and bioinformatic predictions. The pac gene cluster is unique to S. pacifica and found in only two of the 119 Salinispora genomes analyzed across nine species. Comparative analyses of biosynthetic gene clusters encoding the production of related manumycin-type compounds revealed genetic differences in accordance with the unique pacificamide structure. Further queries of manumycin-type gene clusters from public databases revealed their limited distribution across the phylum Actinobacteria and orphan diversity that suggests additional products remain to be discovered in this compound class. Production of the known metabolite triacsin D is also reported for the first time from the genus Salinispora. This study adds two classes of compounds to the natural product collective isolated from the genus Salinispora, which has proven to be a useful model for natural product research.

Autologous bone grafts are currently the standard in orthopedic surgery despite limited donor sources and the prevalence of donor site morbidity. Other alternatives such as allografts are more readily available than autografts but have lower rates of graft incorporation. Here, we propose a novel graft alternative consisting of an injectable poly(propylene fumarate) (PPF) and poly(propylene fumarate-co-caprolactone) P(PF- co -CL) copolymer with a recombinant human bone morphogenetic protein-2 (rhBMP-2)/vascular epithelial growth factor (VEGF) release system accompanied by hydroxyapatite (HA). The efficacy of scaffold formulations was studied using a standard, bilateral, L-level (L5-L6) posterolateral transverse spinal fusion using New Zealand white rabbits. Rabbits were divided into 4 experimental groups: group I, negative control; group II, autograft (positive control); group III, injectable PPF scaffold with rhBMP-2/VEGF release system and HA; group IV, injectable P(PF- co -CL)scaffold with rhBMP-2/VEGF release system and HA. Spines were harvested at 6 weeks and 12 weeks after surgery, and spinal fusions were assessed using manual palpation, radiographic analysis, micro-computed tomography (μCT) assessment, and histologic analysis. Of the 4 experimental groups, the injectable P(PF- co -CL) scaffold displayed superior initial strength and faster degradation than scaffolds constructed from PPF alone and facilitated the fusion of lateral processes in the rabbit standard posterolateral spinal fusion model. The results obtained from manual palpation, radiology, and μCT showed no difference between the P(PF- co -CL) group and the PPF group. However, histologic sections showed more osteogenesis with the new injectable P(PF-co-CL) scaffold. Injectable P(PF-co-CL) polymers showed promising spine fusion abilities in rabbits after 12 weeks of posterolateral implantation. [ABSTRACT FROM AUTHOR]

Substituent effects (SEs) are fundamental for predicting molecular reactivity, while polyene, polyyne and acene derivatives are precursors to compounds with diverse applications. Computations were performed for Y‐R‐X systems, where reaction sites Y=NO2 and O−, substituents X=NO2, CN, Cl, H, OH, NH2, and spacers R=polyene, polyyne (n=1‐5, 10 repeating units) and acene (up to tetracene). The cSAR (charge of the substituent active region) approach allowed to present, for the first time, quantitative relations describing the spacer's electron‐donating and withdrawing properties as a function of n and the spacer type. The electronic properties of the X substituents depend on the type of spacer, its length and the Y group, which is an example of the reverse SE. To describe how the SE between Y and X weakens with n, two approaches were compared: cSAR and SESE (SE stabilization energy). The EDDB (electron density of delocalized bonds) characterize changes in electron delocalization in spacers due to the SE. A new approach – EDDB differential maps – allow to extract the effect of X substitution on the electron delocalization. The charges at spacer's C atoms correlate with cSAR; changes in the slopes confirm the charge transfer by resonance. [ABSTRACT FROM AUTHOR]

In the present study, thermally averaged electronic excitation energies (the so‐called dynamic approach) are quantitatively assessed for a model molecular system composed of a series of increasingly longer chains of simple linear polyenes. The molecular dynamics trajectories are calculated using the semi‐empirical "Geometry, Frequency, Noncovalent, eXtended Tight Binding" (GFN2‐xTB) method, while TD‐DFT vertical excitation energies of selected snapshots are obtained with the spin‐component‐scaled double hybrid density functional SCS‐wPBEPP86. Boltzmann weighted average excitation energies were then calculated in order to take into account the contribution of thermal motions. Excitation energies via the dynamic approach are compared with that of the static approach in which thermal fluctuations are not considered. The differences between the dynamic and the static approaches were found to be around the range −0.01 to +0.01 eV for polyenes up to 44 carbon atoms. This range of errors is relatively small in comparison with typical errors produced by using different density functionals and/or basis sets. Therefore, the electronic excited states of small to medium lengths of linear polyenes (less than 50 carbon atoms) can be safely modeled via the static approach. However, extrapolation of the results to longer polyenes indicates that the difference between both approaches is estimated to be 0.05 eV for polyenes containing 100 carbon atoms, which suggests that considering thermal motions in the calculations of excitation energies is recommended for such long conjugated molecular systems. [ABSTRACT FROM AUTHOR]

Asian ginseng, the root of Panax ginseng C.A. Meyer, occupies a prominent position in the list of best-selling natural products in the world. There are two major types of ginseng roots: white ginseng and red ginseng, each with numerous preparations. White ginseng is prepared by air-drying fresh Asian ginseng roots after harvest. Red ginseng is prepared by steaming roots in controlled conditions using fresh or raw Asian ginseng. Red ginseng is commonly used in Asian countries due to its unique chemical profile, different therapeutic efficacy, and increased stability. Compared with the widespread research on white ginseng, the study of red ginseng is relatively limited. In this paper, after a botanical feature description, the structures of different types of constituents in red ginseng are systematically described, including naturally occurring compounds and those resulting from the steam processing. In red ginseng phytochemical studies, the number of published reports on ginsenosides is significantly higher than that for other constituents. Up to now, 57 ginsenosides have been isolated and characterized in red ginseng. The structural transformation pathways during steaming have been summarized. In comparison with white ginseng, red ginseng also contains other constituents, including polyacetylenes, Maillard reaction products, other types of glycosides, lignans, amino acids, fatty acids, and polysaccharides, which have also been presented. Appropriate analytical methods are necessary for differentiating between unprocessed white ginseng and processed red ginseng. Specific marker compounds and chemical profiles have been used to discriminate red ginseng from white ginseng and adulterated commercial products. Additionally, a brief phytochemical profile comparison has been made between white ginseng and black ginseng, and the latter is another type of processed ginseng prepared from white or red ginseng by steaming several times. In conclusion, to ensure the safe and effective use of red ginseng, phytochemical and analytical studies of its constituents are necessary and even crucial. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine the stability of cetuximab: (1) under "in-use" conditions after dilution to 1 mg/mL in 0.9% sodium chloride in polyolefin bags and (2) as an undiluted solution (5 mg/mL) repackaged in polypropylene bags or kept in the vial after opening. Methods: Ready-to-use 500 mg/100 mL vials of cetuximab solution were diluted to 1 mg/mL in 100 mL bags of 0.9% sodium chloride or repackaged as a 5 mg/mL solution into empty 100 mL bags. Bags and vials were stored at 4°C for 90 days and 25°C for 3 days. A syringe sample of 7 mL was taken from each bag for the initial determinations. The sampled bags were weighed to determine their initial weight and placed under the planned storage conditions. The physicochemical stability of cetuximab was estimated using validated methods. Results: No changes in turbidity, no protein loss, and no changes in cetuximab tertiary structure were observed after 30 days of storage or when subjected to a temperature excursion of 3 days at 25°C and when stored at 4°C for up to 90 days, regardless of the concentrations and batches. The colligative parameters did not change under any of the tested conditions. No evidence of microbial growth was found in bags after 90 days of storage at 4°C. Conclusion: These results support the extended in-use shelf-life of cetuximab vials and bags, which can be cost-effective for healthcare providers. [ABSTRACT FROM AUTHOR]

Propynylidene derivatives of dimethyl malonate and Meldrumʼs acid, as well as cross-conjugated enynones, containing Me3Si, Et3Si, and t-BuMe2Si groups reacted with 4-methyl-, 4-methoxy-, and 4-chloro-benzenethiol under basic conditions to give the corresponding addition products with buta-1,3-diene and penta-1,4-dien-3-one fragments with high stereoselectivity. The thiylation products of enyne derivatives of dimethyl malonate and Meldrumʼs acid retain the trialkylsilyl group, whereas the addition of benzenethiols to 5-(tri-alkylsilyl)-1-phenylpent-1-en-4-yn-3-ones is accompanied by desilylation. Some mechanistic features of the described reactions have been established, and methods for the stereoselective synthesis of sulfur-containing polyunsaturated compounds have been developed. [ABSTRACT FROM AUTHOR]

Polyene pigments represent a major class of pigments in present‐day organisms. Their occurrence in fossils has been frequently discussed, but to date no spectroscopic evidence has been found. Here, we use in situ Raman spectroscopy to examine the chemistry of exceptionally well‐preserved gastropod shells with colour preservation from the Middle Miocene of the Vienna Basin (Austria, Hungary). Raman signals indicative of the presence of intact (i.e. non‐hydrogenated) polyene pigments were obtained from fossil shells with reddish colour patterns, thus revealing the first record of intact polyenes in fossils. The observed Raman values are in good agreement with those of unmethylated (non‐carotenoid) polyenes. Fossil polyene pigments were detected in representatives of the superfamily Cerithioidea, but not in representatives of other gastropod families with colour preservation found at the same localities, demonstrating that the occurrence of polyene pigments is taxon‐specific. Our results show that Raman spectroscopy represents a valuable tool for the non‐destructive screening of rare fossils with colour preservation for the occurrence of polyene pigments. [ABSTRACT FROM AUTHOR]

The asymmetric synthesis of polyunsaturated triene C18:3 n-3 and C18:3 n-6 methoxylated ether lipids (MEL) of the 1-O-alkyl-sn-glycerol type is described as possible structural candidates for a triene C18:3 MEL of an unknown identity found in a mixture of shark and dogfish liver oil. Their C18:3 hydrocarbon chains constitute an all-cis methylene skipped n-3 or n-6 triene framework, along with a methoxyl group at the 2′-position and R-configuration of the resulting stereogenic center. The methoxylated polyenes are attached by an ether linkage to the pro-S hydroxymethyl group of the glycerol backbone. The syntheses were based on the polyacetylene approach that involves a semi-hydrogenation of the resulting triynes. Both syntheses were started from our previously described enantio- and diastereomerically pure isopropylidene-protected glyceryl glycidyl ether, a double-C3 building block that was designed as a head group synthon for the synthesis of various types of MELs. [ABSTRACT FROM AUTHOR]

Sequential formation of a poly-cyclic aromatic hydrocarbon (PAH) dication in the H I regions of the interstellar medium (ISM) is proposed to be a function of internal energy of the doubly ionized PAHs, which, in turn, is dependent on the single- and double-ionization potentials of the system. This sets a limit on the single- and double-ionization energies of the system(s) that can further undergo sequential absorption of two photons, leading to a dication (PAH+2). Here, we report the single-ionization (I+1) and double-ionization (I+2) energies and the I+2/I+1 ratio for some selected PAHs and conjugated polyenes obtained using the Fock space coupled cluster technique, enabling simultaneous consideration of several electronic states of different characters. The I+2 to I+1 ratio bears a constant ratio, giving allowance to determine I+2 from the knowledge of single-ionization (I+1) and vice versa. Our observations are in good agreement with the established literature findings, confirming the reliability of our estimates. The measured single- and double-ionization energies further demonstrate that the sequential formation and fragmentation of a PAH dication in the H I regions of the ISM for systems such as benzene and conjugated polyenes such as ethylene and butadiene are quite unlikely because I+2–I+1 for such system(s) is higher than the available photon energy in the H I regions of the ISM. Present findings may be useful to understand the formation and underlying decay mechanisms of multiply charged ions from PAHs and related compounds that may accentuate the exploration of the phenomenon of high-temperature superconductivity. [ABSTRACT FROM AUTHOR]

Successfully interfacing enzymes and biomachinery with polymers affords on-demand modification and/or programmable degradation during the manufacture, utilization and disposal of plastics, but requires controlled biocatalysis in solid matrices with macromolecular substrates1-7. Embedding enzyme microparticles speeds up polyester degradation, but compromises host properties and unintentionally accelerates the formation of microplastics with partial polymer degradation6,8,9. Here we show that by nanoscopically dispersing enzymes with deep active sites, semi-crystalline polyesters can be degraded primarily via chain-end-mediated processive depolymerization with programmable latency and material integrity, akin to polyadenylation-induced messenger RNA decay10. It is also feasible to achieve processivity with enzymes that have surface-exposed active sites by engineering enzyme-protectant-polymer complexes. Poly(caprolactone) and poly(lactic acid) containing less than 2 weight per cent enzymes are depolymerized in days, with up to 98 per cent polymer-to-small-molecule conversion in standard soil composts and household tap water, completely eliminating current needs to separate and landfill their products in compost facilities. Furthermore, oxidases embedded in polyolefins retain their activities. However, hydrocarbon polymers do not closely associate with enzymes, as their polyester counterparts do, and the reactive radicals that are generated cannot chemically modify the macromolecular host. This study provides molecular guidance towards enzyme-polymer pairing and the selection of enzyme protectants to modulate substrate selectivity and optimize biocatalytic pathways. The results also highlight the need for in-depth research in solid-state enzymology, especially in multi-step enzymatic cascades, to tackle chemically dormant substrates without creating secondary environmental contamination and/or biosafety concerns.

Systematic evaluation of 1,5-dienes bearing 3,3-electron-withdrawing groups and 4-methylation results in the discovery of a Cope rearrangement for Meldrum's acid-containing substrates that have unexpectedly favorable kinetic and thermodynamic profiles. The protocol is quite general due to a concise and convergent synthesis from abundant starting materials. Furthermore, products with an embedded Meldrum's acid moiety are prepared, which, in turn, can yield complex amides under neutral conditions. We have now expanded the scope of the reductive Cope rearrangement, which, via chemoselective reduction, can promote thermodynamically unfavorable [3,3] sigmatropic rearrangements of 3,3-dicyano-1,5-dienes to form reduced Cope rearrangement products. The Cope rearrangement is found to be stereospecific and can yield enantioenriched building blocks when chiral, nonracemic 1,3-disubstituted allylic electrophiles are utilized. We expand further the use of Cope rearrangements for the synthesis of highly valuable building blocks for complex- and drug-like molecular synthesis.

Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic Candida species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in Candida species. Resistance can be conferred via gain-of-function mutations in target pathway genes or their transcriptional regulators. Therefore, an overview of the known gene mutations is presented for the following antifungals: azoles (fluconazole, voriconazole, posaconazole and itraconazole), echinocandins (caspofungin, anidulafungin and micafungin), polyenes (amphotericin B and nystatin) and 5-fluorocytosine (5-FC). The following mutation hot spots were identified: (1) ergosterol biosynthesis pathway mutations (ERG11 and UPC2), resulting in azole resistance; (2) overexpression of the efflux pumps, promoting azole resistance (transcription factor genes: tac1 and mrr1; transporter genes: CDR1, CDR2, MDR1, PDR16 and SNQ2); (3) cell wall biosynthesis mutations (FKS1, FKS2 and PDR1), conferring resistance to echinocandins; (4) mutations of nucleic acid synthesis/repair genes (FCY1, FCY2 and FUR1), resulting in 5-FC resistance; and (5) biofilm production, promoting general antifungal resistance. This review also provides a summary of standardized inhibitory breakpoints obtained from international guidelines for prominent Candida species. Notably, N. glabrata, P. kudriavzevii and C. auris demonstrate fluconazole resistance. [ABSTRACT FROM AUTHOR]

New antifungal agents are needed to overcome limitations of available ones such as poor pharmacokinetic traits, toxicity, drug-drug interactions, limited clinical efficacy, and emerging antifungal resistance. New antifungal drugs belong to well-known families (azoles, polyenes, or beta-d-glucan synthase inhibitors) or to drug families showing completely new mechanisms of action. Some drugs have a head start in terms of potential to reach the clinical setting and are here reviewed. [ABSTRACT FROM AUTHOR]

Reactive oxidant species (ROS) are unstable, highly reactive molecules that are produced by cells either as byproducts of metabolism or synthesized by specialized enzymes. ROS can be detrimental, e.g., by damaging cellular macromolecules, or beneficial, e.g., by participating in signaling. An increasing body of evidence shows that various fungal species, including both yeasts and molds, increase ROS production upon exposure to the antifungal drugs currently used in the clinic: azoles, polyenes, and echinocandins. However, the implications of these findings are still largely unclear due to gaps in knowledge regarding the chemical nature, molecular origins, and functional consequences of these ROS. Because the detection of ROS in fungal cells has largely relied on fluorescent probes that lack specificity, the chemical nature of the ROS is not known, and it may vary depending on the specific fungus-drug combination. In several instances, the origin of antifungal drug-induced ROS has been identified as the mitochondria, but further experiments are necessary to strengthen this conclusion and to investigate other potential cellular ROS sources, such as the ER, peroxisomes, and ROS-producing enzymes. With respect to the function of the ROS, several studies have shown that they contribute to the drugs' fungicidal activities and may be part of drug-induced programmed cell death (PCD). However, whether these "pro-death" ROS are a primary consequence of the antifungal mechanism of action or a secondary consequence of drug-induced PCD remains unclear. Finally, several recent studies have raised the possibility that ROS induction can serve an adaptive role, promoting antifungal drug tolerance and the evolution of drug resistance. Filling these gaps in knowledge will reveal a new aspect of fungal biology and may identify new ways to potentiate antifungal drug activity or prevent the evolution of antifungal drug resistance. [ABSTRACT FROM AUTHOR]

BACKGROUND: The International Agency for Research on Cancer (IARC) Monographs program assembles expert working groups who publish a critical review and evaluation of data on agents of interest. These comprehensive reviews provide a unique opportunity to identify research needs to address classification uncertainties. A multidisciplinary expert review and workshop held in 2009 identified research gaps and needs for 20 priority occupational chemicals, metals, dusts, and physical agents, with the goal of stimulating advances in epidemiological studies of cancer and carcinogen mechanisms. Overarching issues were also described. OBJECTIVES: In this commentary we review the current status of the evidence for the 20 priority agents identified in 2009. We examine whether identified Research Recommendations for each agent were addressed and their potential impact on resolving classification uncertainties. METHODS: We reviewed the IARC classifications of each of the 20 priority agents and identified major new epidemiological and human mechanistic studies published since the last evaluation. Information sources were either the published Monograph for agents that have been reevaluated or, for agents not yet reevaluated, Advisory Group reports and literature searches. Findings are described in view of recent methodological developments in Monographs evidence evaluation processes. DISCUSSION: The majority of the 20 priority agents were reevaluated by IARC since 2009. The overall carcinogen classifications of 9 agents advanced, and new cancer sites with either “sufficient” or “limited” evidence of carcinogenicity were also identified for 9 agents. Examination of published findings revealed whether evidence gaps and Research Recommendations have been addressed and highlighted remaining uncertainties. During the past decade, new research addressed a range of the 2009 recommendations and supported updated classifications for priority agents. This supports future efforts to systematically apply findings of Monograph reviews to identify research gaps and priorities relevant to evaluation criteria established in the updated IARC Monograph Preamble. [ABSTRACT FROM AUTHOR]